%0 Journal Article
%T tRNA修饰酶TiaS蛋白结构与功能研究及其锌指的潜在应用
Research on the Structure and Function of tRNA-Modifying Enzyme TiaS and Potential Applications of Its Zinc Ribbon
%A 董建树
%J Biophysics
%P 10-21
%@ 2330-1694
%D 2021
%I Hans Publishing
%R 10.12677/BIPHY.2021.91002
%X 含有锌指的TiaS (tRNAIle2 agmatidine synthetase)蛋白是来自古菌的酶，具有四个结构域，功能是利用ATP水解释放的能量在tRNAIle2反密码子CAU的简并碱基胞嘧啶Cyt34的2’碳原子上面加上胍基丁胺Agmatine修饰，从而让tRNAIle2成熟不识别AUG，而正确识别AUA密码子。单独TiaS蛋白，TiaS蛋白与tRNA复合物结构已经解析，酶催化修饰的分子机制获得了较深入解读。生化实验表明，TiaS蛋白N端三个结构域具有催化活性，TiaS为焦磷酸酶，可以水解ATP。并且TiaS蛋白的N端结构域可以起到激酶的作用，自磷酸化Thr18氨基酸残基。C端锌指距离酶核心较远，对于识别结合底物具有重要作用。本文总结TiaS蛋白研究进展。对于TiaS蛋白的深入研究，将为深入理解酶催化机制，为酶的工程改造，为锌指的工程改造开辟思路。包括锌指与CRISPR/Cas在内的靶向核酸元件在生命医药和研究领域有广泛应用，TiaS蛋白锌指结构新特性的研究也为基于锌指的靶向核酸组件设计打下基础。
Archaeal TiaS (tRNAIle2 agmatidine synthetase) protein is a zinc-ribbon containing four-domain tRNAIle2 modifying enzyme, which is able to hydrolyze ATP and modify the 2’carbon of the wobble position cytosine 34 with Agmatine (Agm). The modification is essential for tRNAIle2 maturation and thus for accurate deciphering of AUA codon. The enzyme core consisting of the N-terminal three domains is responsible for the catalytic activity. The C-terminal zinc ribbon domain (ZRD) is far away from the enzyme core, and plays important role in substrate tRNA recognition and discrimination. Further research of TiaS will provide significant insight into the mechanism of enzyme catalysis and pave ways for enzyme engineering. Zinc finger engineering and targetable nucleases (by using zinc fingers or CRISPR/Cas) engineering have wide applications ranging from research to medicine. New characteristics about zinc ribbon and zinc ribbon-nucleic acid interaction may help future designs of targetable proteins for applications in genetic modulation, genome manipulation or therapeutics research.
%K 锌指，tRNA修饰，TiaS蛋白，酶催化，核酸靶向
Zinc Ribbon
%K tRNA Modification
%K TiaS Protein
%K Enzymatic Catalysis
%K Nucleic Acid Targeting
%U http://www.hanspub.org/journal/PaperInformation.aspx?PaperID=40718